Regioselective deuterium labeling of estrone and catechol estrogen metabolites

•A new method for regioselective deuterium labeling of the estrogen A ring has been developed.•1-Deutrioestrone has been synthesized, regioselectively, in a one-pot procedure.•The deuterium labeling uses t-butyl alcohol as an exchange catalyst.•A new procedure for regioselective labeling of catechol estrogens at either the 1- or 2-positions has been developed.

Increased exposure to estrogens and estrogen metabolites is linked with increased rates of breast, ovarian and other human cancers. Metabolism of estrogen can led to formation of electrophilic o-quinones capable of binding to DNA. In order to gain insight into the mechanism of estrogen-induced DNA damage, estrone and catechol estrogens derived from estrone, have been regioselectively labeled with deuterium at the 1-position. Estrone-1-d, estrone-1,2,4-d3, 4-hydroxyestrone-1-d and 2-hydroxyestrone-1-d have been synthesized with or without deuteriums at the 16-position. The key labeling step involves deuterated trifluoroacetic acid exchange catalyzed by t-butyl alcohol. This economical, straightforward labeling technique makes available a range of estrone compounds containing deuterium at the 1-position.

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